Genetic variability of the retromer cargo recognition complex in parkinsonism.
作者信息
Gustavsson Emil K, Guella Ilaria, Trinh Joanne, Szu-Tu Chelsea, Rajput Alex, Rajput Ali H, Steele John C, McKeown Martin, Jeon Beom S, Aasly Jan O, Farrer Matthew J
机构信息
Djavad Mowafaghian Centre for Brain Health, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology, St. Olav's Hospital, Trondheim, Norway.
出版信息
Mov Disord. 2015 Apr;30(4):580-4. doi: 10.1002/mds.26104. Epub 2014 Dec 5.
BACKGROUND
A pathogenic mutation (VPS35 p.D620N) within the retromer complex has been shown to segregate with late-onset Parkinson's disease (PD). Several studies have subsequently detected the mutation in patients with PD and not in controls.
METHODS
Mutation screening of the coding regions of the retromer cargo recognition complex genes (VPS26A/B, VPS29, and VPS35) was carried out in patients with PD (n = 396), atypical parkinsonism (n = 229), and in 368 controls.
RESULTS
Overall, we identified five rare nonsynonymous mutations in VPS26A and one in VPS35; none were observed in VPS26B or VPS29. Three VPS26A variants (p.K93E, p.M112V, and p.K297X), identified in patients with atypical parkinsonism, were not observed in controls from this study (n = 368) or from publically available data sets (n = 4,426).
CONCLUSION
Our results support the hypothesis that rare variants in the retromer complex genes may be involved in the development of parkinsonism, although further studies are warranted before any solid conclusions can be drawn.
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